How to manage elevated liver enzymes?

Management of Elevated Liver Enzymes

The most effective approach to normalize elevated liver enzymes is to identify and treat the underlying cause, with lifestyle modifications being the first-line intervention for the most common cause, non-alcoholic fatty liver disease (NAFLD). 1, 2

Initial Evaluation

Diagnostic Workup

1. Core liver panel assessment:

   • Complete liver enzyme profile (AST, ALT, alkaline phosphatase, GGT, bilirubin)
   • Viral hepatitis screening (HBV, HCV)
   • Autoimmune markers (IgG, autoantibodies)
   • Iron studies (ferritin, transferrin saturation)
   • Assess for metabolic syndrome components 1, 2

2. Risk stratification:

   • Calculate fibrosis risk using FIB-4 score:
     • <1.3: Low risk
     • 1.3-2.67: Intermediate risk

     • 2.67: High risk 2

3. Imaging:

   • Abdominal ultrasound as primary screening modality 1

Management Based on Etiology

For NAFLD (Most Common Cause)

1. Lifestyle Modifications:

   • Weight loss: Target 3-5% of body weight to improve steatosis; 7-10% to improve necroinflammation 1, 2
   • Diet: Mediterranean diet pattern with higher monounsaturated fats, lower carbohydrates, reduced fructose intake 1, 2
   • Exercise: 150-300 minutes/week of moderate-intensity physical activity 1, 2
   • Alcohol: Complete abstinence or strict limitation 1

2. Metabolic Control:

   • Optimize management of diabetes, hypertension, and dyslipidemia
   • For patients with diabetes, consider medications that benefit both diabetes and NAFLD (e.g., GLP-1 receptor agonists, pioglitazone) 2, 3

3. Medication Review:

   • Discontinue hepatotoxic medications and supplements 1
   • Review all over-the-counter medications 4

For Other Causes

1. Alcoholic Liver Disease:

   • Complete abstinence from alcohol 1, 5

2. Viral Hepatitis:

   • Refer to specialist for antiviral therapy 1

3. Autoimmune Hepatitis:

   • Refer to specialist for immunosuppressive therapy 1

4. Drug-Induced Liver Injury:

   • Discontinue offending agent 1, 4

5. Immune Checkpoint Inhibitor-Related Hepatitis:

   • Grade-specific management with steroids and/or immunosuppressants 1

Monitoring

1. Laboratory Follow-up:

   • Liver enzymes every 3-6 months initially
   • Lipid profile and glucose/HbA1c every 6 months 2

2. Fibrosis Assessment:

   • Low risk: Repeat every 2-3 years
   • Intermediate/high risk: Annual follow-up 2

Referral Criteria

1. Immediate referral:

   • Clinical jaundice
   • Suspected hepatic or biliary malignancy 1

2. Specialist referral:

   • Evidence of advanced fibrosis (FIB-4 >2.67)
   • AST/ALT >5x upper limit of normal
   • Failed response to initial management after 6 months 1, 2

Important Considerations

• Elevated liver enzymes can be transient, but 75% remain abnormal at 2 years if the underlying cause is not addressed 1
• NAFLD with elevated liver enzymes carries significant risk of developing end-stage liver disease and is associated with lower survival in patients with NASH 6
• Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term 6
• Progression of liver fibrosis is associated with weight gain, insulin resistance, and hepatic fatty infiltration 6

Common Pitfalls to Avoid

1. Assuming mildly elevated enzymes are benign without proper evaluation
2. Focusing only on liver enzymes without addressing metabolic risk factors
3. Recommending rapid weight loss (>1 kg/week), which can worsen portal inflammation and fibrosis 1
4. Failing to screen for other chronic liver diseases that may coexist with NAFLD 1
5. Overlooking extrahepatic causes of elevated liver enzymes 7, 5